TLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells

Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani and Kensuke Miyake ()
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Shin-Ichiroh Saitoh: The Institute of Medical Science, The University of Tokyo
Fumiko Abe: The University of Tokyo
Atsuo Kanno: The Institute of Medical Science, The University of Tokyo
Natsuko Tanimura: The Institute of Medical Science, The University of Tokyo
Yoshiko Mori Saitoh: The Institute of Medical Science, The University of Tokyo
Ryutaro Fukui: The Institute of Medical Science, The University of Tokyo
Takuma Shibata: The Institute of Medical Science, The University of Tokyo
Katsuaki Sato: University of Miyazaki
Takeshi Ichinohe: The University of Tokyo
Mayumi Hayashi: Ltd., 1-16-13 Kitakasai
Kazuishi Kubota: Ltd., 1-16-13 Kitakasai
Hiroko Kozuka-Hata: The University of Tokyo
Masaaki Oyama: The University of Tokyo
Yorifumi Kikko: The University of Tokyo
Toshiaki Katada: The University of Tokyo
Kenji Kontani: The University of Tokyo
Kensuke Miyake: The Institute of Medical Science, The University of Tokyo

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC–pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7+ lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7. The type I interferon signaling molecules TRAF3, IKKα, and mTORC1 are constitutively associated in pDCs. TLR7 localizes to mTORC1 and induces association of TRAF3 with the upstream molecule TRAF6. Finally, type I interferons are secreted in the vicinity of cell–cell contacts between clustered pDCs. These results suggest that TLR7 needs to move to the cell periphery to induce robust type I interferon responses in pDCs.

Date: 2017
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DOI: 10.1038/s41467-017-01687-x

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